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Context

Inhibitors of Trypanosoma cruzi with novel mechanisms of action are urgently required to diversify the current clinical and pre-clinical pipelines. Increasing the number and diversity of hits available for assessment at the beginning of the discovery process will help to achieve this aim.

We have evaluated multiple hits generated from a high-throughput screen of over 300,000 compounds to identify inhibitors of T. cruzi. These studies have resulted in the discovery of two novel series currently in lead optimisation. Lead compounds from these series potently and selectively inhibit growth of T. cruzi in vitro and the most advanced compound is orally active in a sub-chronic mouse model of T. cruzi infection.

High-throughput screening of novel compound collections has an important role to play in diversifying the trypanosomatid drug discovery portfolio. A new T. cruzi inhibitor series with good drug-like properties and promising in vivo efficacy has been identified through this process.

About DNDi

Drugs for Neglected Diseases initiative (DNDi) is a collaborative, patients’ needs-driven, non-profit drug research and development (R&D) organization that is developing new treatments for neglected patients.

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